Jeffrey Yap - Academia.edu (original) (raw)

Papers by Jeffrey Yap

Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2006

1Cancer Imaging Program, National Cancer Institute, National Institutes of Health, Bethesda, Mary... more 1Cancer Imaging Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland; 2Division of Nuclear Medicine, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah; 3Department of Radiology, University of California, San Francisco, California; 4Division of Nuclear Medicine, Department of Radiology, University of Iowa, Iowa City, Iowa; 5Division of Nuclear Medicine, Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania; 6Department of Nuclear Medicine and PET Research, VU University Medical Centre, Amsterdam, The Netherlands; 7Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York; 8Division of Nuclear Medicine, University of Washington, Seattle, Washington; 9Mallinckrodt Institute of Radiology, St. Louis, Missouri; and 10Department of Radiology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts

UNLABELLED Currently, there are no available means in the United States to document objectively t... more UNLABELLED Currently, there are no available means in the United States to document objectively the location and extent of amyloid deposits in patients with systemic forms of amyloidosis. To address this limitation, we have developed a novel diagnostic strategy, namely, the use of a radiolabeled fibril-reactive murine monoclonal antibody (mAb) as an amyloid-specific imaging agent. The goal of this study was to determine the pharmacokinetics, biodistribution, and ability of this reagent to target the type of amyloid that is formed from immunoglobulin light chains, that is, AL. METHODS Subcutaneous tumors (amyloidomas) were induced in BALB/c mice by injection of human AL fibrils. The IgG1 mAb designated 11-1F4 and an isotype-matched control antibody were radioiodinated, and the pharmacokinetics and localization of these reagents were determined from blood and tissue samples. Amyloidoma-bearing animals that received (125)I- or (124)I-labeled antibodies were imaged by whole-body small-a...

Part I: PET Image Reconstruction Focus: Impact of clinically available reconstruction methods on ... more Part I: PET Image Reconstruction Focus: Impact of clinically available reconstruction methods on image quality 2D versus 3D Imaging Scatter and Randoms Correction Attenuation Correction Filtered BackProjection Statistical (Iterative) Reconstruction Randoms Corrections Methods delayed window (128 ns), on-line subtraction delayed window, off-line subtraction of smoothed delayeds (Casey) estimate from R = k x singles2 x (2τ) extrapolation from outside object

Cancer Medicine

This is an open access article under the terms of the Creative Commons Attribution License, which... more This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Journal of Clinical Oncology

10507 Background: Most GISTs have activating mutations of KIT/PDGFRA, with rare cases of B-RAF/RA... more 10507 Background: Most GISTs have activating mutations of KIT/PDGFRA, with rare cases of B-RAF/RAS mutations. 15% of GIST in adults and 85% in children are WT and commonly have high expression of IGF1R likely due to loss of succinate dehydrogenase (SDH) function. We tested the clnical benefit of linsitinib (L), an oral TKI with in vitro efficacy against IGF1R in WT GIST patients (pts). Methods: A multi-center phase II trial of L using Clopper-Pearson two-stage design was conducted by SARC. All eligible pts signed consent, were >18 yo, had KIT/ PDGFRA WT GIST, RECIST1.1 measurable disease, ECOG PS of 0-2, and adequate organ function including: fasting glucose of < 150 mg/dL, hemoglobin A1c < 7%, and a QTcF interval of < 450 msec. The trial's primary endpoint was objective response rate (ORR) and secondary endpoints were clinical benefit rate (CBR): CR, PR and SD≥9 mos, and qualitative and quantitative FDG metabolic response (MR) at 8 weeks. Results: 20 pts were accrued to stage I of the study from 11/12-4/...

American journal of nuclear medicine and molecular imaging, 2018

Amyloid beta (Aβ) plaques are not specific to Alzheimer's disease and occur with aging and ne... more Amyloid beta (Aβ) plaques are not specific to Alzheimer's disease and occur with aging and neurodegenerative disorders. Soluble brain Aβ may be neuroprotective and increases in response to neuroinflammation. Sepsis is associated with neurocognitive compromise. The objective was to determine, in a rat endotoxemia model of sepsis, whether neuroinflammation and soluble Aβ production are associated with Aβ plaque and hyperphosphorylated tau deposition in the brain. Male Sprague Dawley rats received a single intraperitoneal injection of 10 mg/kg of lipopolysaccharide endotoxin (LPS). Brain and blood levels of IL-1β, IL-6, and TNFα and cortical microglial density were measured in LPS-injected and control animals. Soluble brain Aβ and p-tau were compared and Aβ plaques were quantified and characterized. Brain uptake of [F]flutemetamol was measured by phosphor imaging. LPS endotoxemia resulted in elevations of cytokines in blood and brain. Microglial density was increased in LPS-treated...

Molecular cancer research : MCR, Dec 29, 2017

Synovial sarcomas are deadly soft-tissue malignancies associated with t(X;18) balanced chromosoma... more Synovial sarcomas are deadly soft-tissue malignancies associated with t(X;18) balanced chromosomal translocations. Expression of the apoptotic regulator BCL2 is prominent in synovial sarcomas and has prompted the hypothesis that synovial sarcomagenesis may depend on it. Herein, it is demonstrated that Bcl2 overexpression enhances synovial sarcomagenesis in an animal model. Further, we determined increased familial clustering of human synovial sarcoma patients with victims of other BCL2-associated malignancies in the Utah Population Database. Conditional genetic disruption of Bcl2 in mice also led to reduced sarcomagenesis. Pharmacologic inhibition specific to BCL2 had no demonstrable efficacy against human synovial sarcoma cell lines or mouse tumors. However, targeting BCLxL in human and mouse synovial sarcoma with the small molecule BH3 domain inhibitor, BXI-72, achieved significant cytoreduction and increased apoptotic signaling. Thus, the contributory role of BCL2 in synovial sar...

Journal of medical imaging (Bellingham, Wash.), 2017

An important challenge to using fluorodeoxyglucose-positron emission tomography (FDG-PET) in clin... more An important challenge to using fluorodeoxyglucose-positron emission tomography (FDG-PET) in clinical trials of brain tumor patients is to identify malignant regions whose metabolic activity shows significant changes between pretreatment and a posttreatment scans in the presence of high normal brain background metabolism. This paper describes a semiautomated processing and analysis pipeline that is able to detect such changes objectively with a given false detection rate. Image registration and voxelwise comparison of the pre- and posttreatment images were performed. A key step is adjustment of the observed difference by the estimated background change at each voxel, thereby overcoming the confounding effect of spatially heterogeneous metabolic activity in the brain. Components of the proposed method were validated via phantom experiments and computer simulations. It achieves a false response volume accuracy of 0.4% at a significance threshold of 3 standard deviations. It is shown t...

Journal of neuro-oncology, Jan 30, 2016

Glioblastoma (GBM) is an incurable brain tumor characterized by the expression of pro-angiogenic ... more Glioblastoma (GBM) is an incurable brain tumor characterized by the expression of pro-angiogenic cytokines. A recent phase II clinical trial studied VEGF Trap in adult patients with temozolomide-resistant GBM. We sought to explore changes in [(18)F]Fluorodeoxyglucose positron emission tomography (FDG-PET) or magnetic resonance imaging (MRI) in trial participants correlating these changes with disease response. FDG-PET and MRI images obtained before and after the first dose of VEGF Trap were spatially co-registered. Regions of interest on each image slice were combined to produce a volume of interest representative of the entire tumor. Percent and absolute changes in maximum FDG-avidity, mean apparent diffusion coefficient (ADC), Ktrans, and Ve were calculated per lesion. Among the 12 participants that underwent dynamic contrast enhanced MRI (DCE-MRI), there were large, statistically significant reductions in Ktrans and Ve (median difference = -41.8 %, p < 0.02 and -42.6 %, p <...

Society of Nuclear Medicine Annual Meeting Abstracts, May 1, 2008

Society of Nuclear Medicine Annual Meeting Abstracts, May 1, 2010

Society of Nuclear Medicine Annual Meeting Abstracts, May 1, 2010

Society of Nuclear Medicine Annual Meeting Abstracts, May 1, 2007

PET with 15O-labeled water allows noninvasive quantification of myocardial blood flow (MBF) at ba... more PET with 15O-labeled water allows noninvasive quantification of myocardial blood flow (MBF) at baseline and during pharmaco logically induced hyperemia to assess the coronary vasodilator reserve (CVR = hyperemic/baseline MBF). Despite widespread use of PET, its reproducibility during one study session has not been tested. Intravenous adenosine (Ado), a powerful coronary vasodilator with a very short decay time, is commonly used for the induction of hyperemia. However, it is not known whether Ado can induce tachyphylaxis after short-term repetitive administra tion. In this study, we aimed to test the reproducibility of PET assessment of CVR during Ado-induced hyperemia. Methods: In 21 healthy volunteer men, baseline and Ado MBF were mea sured twice using PET with 15O-labeledwater to obtain two CVR assessments within 1 h. Results: There was no significant difference between the two baselines (0.89 ±0.14versus 0.99 ± 0.15 mL/min/g, mean difference 13% ±11%) or between the two hyperemic MBFs (3.51 ±0.45 versus 3.83 ±0.49 mL/min/g, mean difference 10% ±14%),resulting in comparable values of CVR (4.05 ±0.75 versus 3.93 ±0.72, mean difference 2% ± 15%). The repeatability coefficient for MBF was 0.17 mL/min/g at baseline and 0.94 mL/min/g during hyperemia. The repeatability coefficient of the rate pressure product (RPP) was lower at baseline (1,304 mm Hg x beat/min) than during hyperemia (3,448 mm Hg x beat/min). Conclusion: Repeated measure ments of MBF and CVR during the same study session were not significantly different, demonstrating the validity of the technique. The larger variability of hyperemic flow, as indicated by the larger repeatability coefficient, was paralleled by a greater variability of the RPP. This could mean that the greater variability of MBF during stress is more likely due to a variable response to Ado rather than to a measurement error.

Society of Nuclear Medicine Annual Meeting Abstracts, May 1, 2010

Journal of Nuclear Medicine, Apr 1, 2000

Society of Nuclear Medicine Annual Meeting Abstracts, May 1, 2014

Society of Nuclear Medicine Annual Meeting Abstracts, May 1, 2010

Society of Nuclear Medicine Annual Meeting Abstracts, May 1, 2008

Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2006

1Cancer Imaging Program, National Cancer Institute, National Institutes of Health, Bethesda, Mary... more 1Cancer Imaging Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland; 2Division of Nuclear Medicine, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah; 3Department of Radiology, University of California, San Francisco, California; 4Division of Nuclear Medicine, Department of Radiology, University of Iowa, Iowa City, Iowa; 5Division of Nuclear Medicine, Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania; 6Department of Nuclear Medicine and PET Research, VU University Medical Centre, Amsterdam, The Netherlands; 7Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York; 8Division of Nuclear Medicine, University of Washington, Seattle, Washington; 9Mallinckrodt Institute of Radiology, St. Louis, Missouri; and 10Department of Radiology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts

UNLABELLED Currently, there are no available means in the United States to document objectively t... more UNLABELLED Currently, there are no available means in the United States to document objectively the location and extent of amyloid deposits in patients with systemic forms of amyloidosis. To address this limitation, we have developed a novel diagnostic strategy, namely, the use of a radiolabeled fibril-reactive murine monoclonal antibody (mAb) as an amyloid-specific imaging agent. The goal of this study was to determine the pharmacokinetics, biodistribution, and ability of this reagent to target the type of amyloid that is formed from immunoglobulin light chains, that is, AL. METHODS Subcutaneous tumors (amyloidomas) were induced in BALB/c mice by injection of human AL fibrils. The IgG1 mAb designated 11-1F4 and an isotype-matched control antibody were radioiodinated, and the pharmacokinetics and localization of these reagents were determined from blood and tissue samples. Amyloidoma-bearing animals that received (125)I- or (124)I-labeled antibodies were imaged by whole-body small-a...

Part I: PET Image Reconstruction Focus: Impact of clinically available reconstruction methods on ... more Part I: PET Image Reconstruction Focus: Impact of clinically available reconstruction methods on image quality 2D versus 3D Imaging Scatter and Randoms Correction Attenuation Correction Filtered BackProjection Statistical (Iterative) Reconstruction Randoms Corrections Methods delayed window (128 ns), on-line subtraction delayed window, off-line subtraction of smoothed delayeds (Casey) estimate from R = k x singles2 x (2τ) extrapolation from outside object

Cancer Medicine

This is an open access article under the terms of the Creative Commons Attribution License, which... more This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Journal of Clinical Oncology

10507 Background: Most GISTs have activating mutations of KIT/PDGFRA, with rare cases of B-RAF/RA... more 10507 Background: Most GISTs have activating mutations of KIT/PDGFRA, with rare cases of B-RAF/RAS mutations. 15% of GIST in adults and 85% in children are WT and commonly have high expression of IGF1R likely due to loss of succinate dehydrogenase (SDH) function. We tested the clnical benefit of linsitinib (L), an oral TKI with in vitro efficacy against IGF1R in WT GIST patients (pts). Methods: A multi-center phase II trial of L using Clopper-Pearson two-stage design was conducted by SARC. All eligible pts signed consent, were >18 yo, had KIT/ PDGFRA WT GIST, RECIST1.1 measurable disease, ECOG PS of 0-2, and adequate organ function including: fasting glucose of < 150 mg/dL, hemoglobin A1c < 7%, and a QTcF interval of < 450 msec. The trial's primary endpoint was objective response rate (ORR) and secondary endpoints were clinical benefit rate (CBR): CR, PR and SD≥9 mos, and qualitative and quantitative FDG metabolic response (MR) at 8 weeks. Results: 20 pts were accrued to stage I of the study from 11/12-4/...

American journal of nuclear medicine and molecular imaging, 2018

Amyloid beta (Aβ) plaques are not specific to Alzheimer's disease and occur with aging and ne... more Amyloid beta (Aβ) plaques are not specific to Alzheimer's disease and occur with aging and neurodegenerative disorders. Soluble brain Aβ may be neuroprotective and increases in response to neuroinflammation. Sepsis is associated with neurocognitive compromise. The objective was to determine, in a rat endotoxemia model of sepsis, whether neuroinflammation and soluble Aβ production are associated with Aβ plaque and hyperphosphorylated tau deposition in the brain. Male Sprague Dawley rats received a single intraperitoneal injection of 10 mg/kg of lipopolysaccharide endotoxin (LPS). Brain and blood levels of IL-1β, IL-6, and TNFα and cortical microglial density were measured in LPS-injected and control animals. Soluble brain Aβ and p-tau were compared and Aβ plaques were quantified and characterized. Brain uptake of [F]flutemetamol was measured by phosphor imaging. LPS endotoxemia resulted in elevations of cytokines in blood and brain. Microglial density was increased in LPS-treated...

Molecular cancer research : MCR, Dec 29, 2017

Synovial sarcomas are deadly soft-tissue malignancies associated with t(X;18) balanced chromosoma... more Synovial sarcomas are deadly soft-tissue malignancies associated with t(X;18) balanced chromosomal translocations. Expression of the apoptotic regulator BCL2 is prominent in synovial sarcomas and has prompted the hypothesis that synovial sarcomagenesis may depend on it. Herein, it is demonstrated that Bcl2 overexpression enhances synovial sarcomagenesis in an animal model. Further, we determined increased familial clustering of human synovial sarcoma patients with victims of other BCL2-associated malignancies in the Utah Population Database. Conditional genetic disruption of Bcl2 in mice also led to reduced sarcomagenesis. Pharmacologic inhibition specific to BCL2 had no demonstrable efficacy against human synovial sarcoma cell lines or mouse tumors. However, targeting BCLxL in human and mouse synovial sarcoma with the small molecule BH3 domain inhibitor, BXI-72, achieved significant cytoreduction and increased apoptotic signaling. Thus, the contributory role of BCL2 in synovial sar...

Journal of medical imaging (Bellingham, Wash.), 2017

An important challenge to using fluorodeoxyglucose-positron emission tomography (FDG-PET) in clin... more An important challenge to using fluorodeoxyglucose-positron emission tomography (FDG-PET) in clinical trials of brain tumor patients is to identify malignant regions whose metabolic activity shows significant changes between pretreatment and a posttreatment scans in the presence of high normal brain background metabolism. This paper describes a semiautomated processing and analysis pipeline that is able to detect such changes objectively with a given false detection rate. Image registration and voxelwise comparison of the pre- and posttreatment images were performed. A key step is adjustment of the observed difference by the estimated background change at each voxel, thereby overcoming the confounding effect of spatially heterogeneous metabolic activity in the brain. Components of the proposed method were validated via phantom experiments and computer simulations. It achieves a false response volume accuracy of 0.4% at a significance threshold of 3 standard deviations. It is shown t...

Journal of neuro-oncology, Jan 30, 2016

Glioblastoma (GBM) is an incurable brain tumor characterized by the expression of pro-angiogenic ... more Glioblastoma (GBM) is an incurable brain tumor characterized by the expression of pro-angiogenic cytokines. A recent phase II clinical trial studied VEGF Trap in adult patients with temozolomide-resistant GBM. We sought to explore changes in [(18)F]Fluorodeoxyglucose positron emission tomography (FDG-PET) or magnetic resonance imaging (MRI) in trial participants correlating these changes with disease response. FDG-PET and MRI images obtained before and after the first dose of VEGF Trap were spatially co-registered. Regions of interest on each image slice were combined to produce a volume of interest representative of the entire tumor. Percent and absolute changes in maximum FDG-avidity, mean apparent diffusion coefficient (ADC), Ktrans, and Ve were calculated per lesion. Among the 12 participants that underwent dynamic contrast enhanced MRI (DCE-MRI), there were large, statistically significant reductions in Ktrans and Ve (median difference = -41.8 %, p < 0.02 and -42.6 %, p <...

Society of Nuclear Medicine Annual Meeting Abstracts, May 1, 2008

Society of Nuclear Medicine Annual Meeting Abstracts, May 1, 2010

Society of Nuclear Medicine Annual Meeting Abstracts, May 1, 2010

Society of Nuclear Medicine Annual Meeting Abstracts, May 1, 2007

PET with 15O-labeled water allows noninvasive quantification of myocardial blood flow (MBF) at ba... more PET with 15O-labeled water allows noninvasive quantification of myocardial blood flow (MBF) at baseline and during pharmaco logically induced hyperemia to assess the coronary vasodilator reserve (CVR = hyperemic/baseline MBF). Despite widespread use of PET, its reproducibility during one study session has not been tested. Intravenous adenosine (Ado), a powerful coronary vasodilator with a very short decay time, is commonly used for the induction of hyperemia. However, it is not known whether Ado can induce tachyphylaxis after short-term repetitive administra tion. In this study, we aimed to test the reproducibility of PET assessment of CVR during Ado-induced hyperemia. Methods: In 21 healthy volunteer men, baseline and Ado MBF were mea sured twice using PET with 15O-labeledwater to obtain two CVR assessments within 1 h. Results: There was no significant difference between the two baselines (0.89 ±0.14versus 0.99 ± 0.15 mL/min/g, mean difference 13% ±11%) or between the two hyperemic MBFs (3.51 ±0.45 versus 3.83 ±0.49 mL/min/g, mean difference 10% ±14%),resulting in comparable values of CVR (4.05 ±0.75 versus 3.93 ±0.72, mean difference 2% ± 15%). The repeatability coefficient for MBF was 0.17 mL/min/g at baseline and 0.94 mL/min/g during hyperemia. The repeatability coefficient of the rate pressure product (RPP) was lower at baseline (1,304 mm Hg x beat/min) than during hyperemia (3,448 mm Hg x beat/min). Conclusion: Repeated measure ments of MBF and CVR during the same study session were not significantly different, demonstrating the validity of the technique. The larger variability of hyperemic flow, as indicated by the larger repeatability coefficient, was paralleled by a greater variability of the RPP. This could mean that the greater variability of MBF during stress is more likely due to a variable response to Ado rather than to a measurement error.

Society of Nuclear Medicine Annual Meeting Abstracts, May 1, 2010

Journal of Nuclear Medicine, Apr 1, 2000

Society of Nuclear Medicine Annual Meeting Abstracts, May 1, 2014

Society of Nuclear Medicine Annual Meeting Abstracts, May 1, 2010

Society of Nuclear Medicine Annual Meeting Abstracts, May 1, 2008